Comparative Effects of Glucose-Lowering Medications on Kidney Outcomes in Patients with Type 2 Diabetes

JAMA Internal Medicine: Published on May, 2023

Diabetic kidney disease is the leading cause of chronic kidney disease and end-stage kidney failure in the vast majority of the world. 


This randomized clinical trial evaluated the use of glucose-lowering medications on kidney outcomes.

A total of 5047 patients with type 2 diabetes without kidney disease at baseline and treated with metformin were assigned to treatment with a sulfonylurea, a DPP-4 inhibitor, a GLP-1 receptor agonist, or basal insulin.

In this randomized clinical trial, among people with T2D and predominantly free of kidney disease at baseline, no significant differences in kidney outcomes were observed during 5 years of follow-up when a dipeptidyl peptidase 4 inhibitor, sulfonylurea, glucagonlike peptide 1 receptor agonist, or basal insulin was added to metformin for glycemic control.


At the end of this trial, there were no significant differences in the rates of decreased eGFR, progression of albuminuria, dialysis, kidney transplantation, or death during the 5-year follow-up.

This is important in clinical practice as we tend to tailor therapy toward patient comorbidities. In the absence of kidney disease specifically, treatment should be tailored toward glycemic goals, which can be achieved with different agents.


We have learned through the observations of numerous clinical trials over the past several decades that improving glycemic and blood pressure control, particularly with the use of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB), results in slower progression of albuminuria and reduced incidence of end-stage kidney disease (ESKD).

More recently, the results of three clinical trials demonstrated that sodium glucose co-transporter inhibitors are capable of slowing progression of kidney disease despite intercurrent use of renin–angiotensin system blocking drugs, and independent of glucose control.

Unfortunately, the study was far too brief, despite 5 years of follow-up, to examine hard renal endpoints like ESKD. The majority of patients were at low risk, with excellent kidney function, well-controlled blood pressure, and little or no albuminuria. It could take decades to demonstrate clinical outcome differences between different treatment regimens in patients like these. 

It is likely that SGLT2 inhibitors would prove to be superior to other agents in the prevention of diabetic kidney disease if future comparative clinical trials are conducted. There is data suggesting that SGLT2 inhibitors slow albuminuria progression and loss of GFR in patients with type 2 diabetes and low-grade albuminuria.

Expert opinion is that SGLT2 inhibitors remain a preferred therapeutic consideration in conjunction with metformin in patients with type 2 diabetes at-risk for developing kidney complications, or with established kidney disease.

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This is for informational purposes only. You should consult your clinical textbook for advising your patients.